Genomic analysis reveals a functional role for myocardial trabeculae in adults

Meyer, Hannah V, Dawes, Timothy JW, Serrani, Marta, Bai, Wenjia, Tokarczuk, Pawel, Cai, Jiashen, de Marvao, Antonio, Rueckert, Daniel, Matthews, Paul M, Costantino, Maria L, Birney, Ewan, Cook, Stuart A, O'Regan, Declan P (March 2019) Genomic analysis reveals a functional role for myocardial trabeculae in adults. bioRxiv. p. 553651. (Unpublished)

DOI: 10.1101/553651


Since being first described by Leonardo da Vinci in 1513 it has remained an enigma why the endocardial surfaces of the adult heart retain a complex network of muscular trabeculae - with their persistence thought to be a vestige of embryonic development. For causative physiological inference we harness population genomics, image-based intermediate phenotyping and in silico modelling to determine the effect of this complex cardiovascular trait on function. Using deep learning-based image analysis we identified genetic associations with trabecular complexity in 18,097 UK Biobank participants which were replicated in an independently measured cohort of 1,129 healthy adults. Genes in these associated regions are enriched for expression in the fetal heart or vasculature and implicate loci associated with haemodynamic phenotypes and developmental pathways. A causal relationship between increasing trabecular complexity and both ventricular performance and electrical activity are supported by complementary biomechanical simulations and Mendelian randomisation studies. These findings show that myocardial trabeculae are a previously-unrecognised determinant of cardiovascular physiology in adult humans.

Item Type: Paper
Subjects: diseases & disorders > cardiovascular diseases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > morphological divergence
CSHL Authors:
Communities: CSHL labs > Meyer Lab
Depositing User: Matthew Dunn
Date: 1 March 2019
Date Deposited: 25 Mar 2019 14:02
Last Modified: 25 Mar 2019 14:02

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